Currently, there are approximately 2 million women in the United States living with breast cancer and the disease is the second leading cause of cancer death in women. Approximately 80% of women with metastatic breast cancer will have tumors arise in the bone. Bone is a common site for cancer metastasis, and bone metastases are frequently associated with complications such as hypercalcemia due to osteolysis, nerve compression, intractable bone pain and pathological fractures. The observation that the majority of cancers exhibit target organ preference when they disseminate was first described in a study of the autopsy records of 735 women who died of breast cancer. The study showed that the highest numbers of metastases were found in the ovaries and the skeleton. The progression of breast cancer bone metastases requires the establishment of functional interactions between metastatic breast cancer cells and bone cells. These interactions are presumably mediated by direct cell-cell contact, and/or soluble stimulators that directly or indirectly induce osteoclast formation and activity.
A critical barrier to understanding and treating breast cancer metastasis and other metastatic cancers is the paucity of sensitive and validated biomarkers. The clinical evaluation of bone metastasis in individual cancer patients involves radiographic confirmation of the diagnosis, the investigation of secondary causes of bone loss and the evaluation of clinical bone turnover biomarkers. However, few bone turnover biomarkers for cancer have been demonstrated to have clinical significance. Therefore, the identification of new target molecules useful in the diagnosis and treatment of cancer and other diseases is a continuing need. In addition, methods for evaluating the role that target molecules play in breast cancer are also needed. In particular, detection of cancer-derived gene products from biologic fluids is an important emerging approach to the diagnosis of malignant diseases.